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INTRODUCTION 

This is the Environmental Protection Agency’s (EPA or the Agency) Final Work Plan (FWP) for 

the registration review of imazalil (PC Code 111901) and imazalil sulfate (PC Code 111902). 

This work plan addresses public comments received concerning the Preliminary Work Plan

(PWP), which was posted in the imazalil registration review docket (EPA-HQ-OPP-2013-0305). 

Imazalil is a systemic imidazole fungicide registered for use for control of a variety of fungal 

pathogens. It is used for postharvest treatment of citrus fruits and bananas (imported), seed 

treatment of barley, wheat, and triticale, and ornamental plants in commercial greenhouses. 

Imazalil also has an antimicrobial indoor non-food use: the control of Aspergillus fumigates in 

egg hatching facilities and equipment disinfection. Imazalil has no registered residential uses. 

The Agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review each registered 

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

registration. Changes in science, public policy, and pesticide use practices occur over time. The 

registration review program is intended to make sure that, as the ability to assess risk evolves and 

as policies and practices change, all registered pesticides continue to meet the statutory standard. 

The public phase of registration review begins when the initial docket is opened for each case. 

Information on this program is provided on the Agency’s website.1

The FWP begins with any updates since the PWP was issued. Next is a summary of substantive 

comments received during the public comment period for the PWP concerning anticipated data 

needs, expected risk assessments, or the estimated timeline identified in the PWP, and a 

summary of the Agency’s responses to those comments. This section is followed by registration 

review planned data needs, risk assessments expected to be conducted, and the projected 

registration review timeline for imazalil and imazalil sulfate. Lastly, there is a discussion of next 

steps. 

UPDATES SINCE THE PWP WAS ISSUED 

Since the publication of the PWP, GLN 850.3100 (Earthworm Subchronic Toxicity Test) has 

been removed from the list of data requirements for imazalil. The Agency has received a 

completed 14-day earthworm toxicity study2

 referenced by the European Food Safety Authority 

(EFSA)3

 and is not requesting a new earthworm study at this time. Also, incorrect guideline 

numbers appear in the PWP for the estuarine and freshwater whole sediment chronic invertebrate 

toxicity studies. The GLN numbers provided in the PWP are for acute rather than chronic 

toxicity studies, which are non-guideline. The FWP has been amended to reflect this correction. 

SUMMARY OF COMMENTS AND AGENCY RESPONSES 

During the 60-day public comment period on the Imazalil and Imazalil Sulfate Preliminary Work 

Plan, which opened on Dec 20, 2013 and closed on Feb 18, 2014, the Agency received 4 public 

 

1

 http://www.epa.gov/oppsrrd1/registration_review/ 

2 The toxicity of imazalil to earthworms. Toxicity of imazalil to Eisenia foetida in an artificial soil toxicity test. Janssen 

Pharmaceutica, Study No. R 23 979/L19, April 1986.

3

 EFSA summary document viewable at http://www.efsa.europa.eu/en/efsajournal/doc/1526.pdf.
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comments. Comments on use and usage of imazalil were submitted by the Arizona Pest 

Management Center, California Citrus Quality Council, and the Washington State Pest 

Management Resource Service at Washington State University Tri-Cities (Western IPM Center). 

Comments from the Center for Biological Diversity provided information on accessing imazalil 

data relevant to the protection of endangered species. The comments do not address the 

regulatory timeline, the planned ecological and human health risk assessments described in the 

PWP, or anticipated data requirements for imazalil. In the imazalil PWP, EPA also solicited 

comments on the specific topics of environmental justice, water quality concerns, and trade 

irritants, but no comments or information were received on those issues.

No public comments resulted in changes to the anticipated registration review data needs, risk 

assessments, or timeline. Public comments in their entirety are located in the docket EPA-HQOPP-2013-0305. The Agency thanks all commenters for their comments and will consider the 

information supplied by them as EPA conducts the registration review and makes its registration 

review decision.

PLANNED DATA NEEDS 

Table 1 below summarizes the planned data needs for imazalil based on the Registration Review 

– Preliminary Problem Formulation for Ecological Risk and Environmental Fate, Endangered 

Species, and Drinking Water Assessments for Imazalil and Imazalil Sulfate and the Imazalil and 

Imazalil Sulfate: Human Health Assessment Scoping Document in Support of Registration 

Review. The 90-day inhalation toxicity study (GLN 870.3465) is required for both antimicrobial 

and conventional pesticide uses. All other studies listed in this table are for conventional 

pesticide uses. 

Table 1: Planned Data Needs for the Imazalil & Imazalil Sulfate Registration Review 4

Guideline 

Number5 Study Title Test Material 

Estimated 

Timeframe 

(Months 

from receipt 

of DCI) 

Imazalil – PC Code 111901 

835.1410 Laboratory Volatility6 TEP 12 

835.4100 Aerobic Soil Metabolism TGAI or 

PAIRA 

24 

835.6100 Terrestrial Field Dissipation TGAI 24 

850.1075 Fish Acute Toxicity Test (saltwater only) TGAI 12 

 

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 For studies listed in this table that are requested for both imazalil and imazalil sulfate (all studies listed except 

875.2100: Dislodgeable Foliar Residue Dissipation), data may be bridged between imazalil and imazalil sulfate. 

The preferred test material for all studies is imazalil rather than imazalil sulfate. 5

 On June 27, 2012, EPA announced certain revisions in harmonized guideline series 850 – Ecological Effects Tests 

– including renumbering and other designations or changes for some guideline studies. See “Final Test 

Guidelines; OCSPP 850 Series; Notice of Availability” 77 FR 38282, June 27, 2012. 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0028 6

 Required as Henry’ Law Constant > 10-6 atm·m3·mol-1 and to support greenhouse use (see problem formulation). 

Study must be performed at a pH above 7. 
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Table 1: Planned Data Needs for the Imazalil & Imazalil Sulfate Registration Review 4

Guideline 

Number5 Study Title Test Material 

Estimated 

Timeframe 

(Months 

from receipt 

of DCI) 

850.1400 Fish Early-Life Stage Toxicity Test 

(freshwater) TGAI 12 

850.1730 Fish Bioconcentration Factor TGAI 12 

850.2100 Avian Acute Oral Toxicity (passerine 

species) TGAI 12 

850.3020 Honeybee Acute Contact Toxicity TGAI 12 

850.6100 Environmental Chemistry Method and 

Associated Independent Laboratory 

Validation (soil only) 

TGAI 12 

870.3465 90-day Inhalation Toxicity - Rat7 TGAI 24 

875.2100 Dislodgeable Foliar Residue (DFR) 

Dissipation8 TEP 24 

Nonguideline Honeybee Acute Oral Toxicity9

TGAI 12 

Nonguideline Whole Sediment Life Cycle Toxicity Test 

with Estuarine Invertebrates 

TGAI 24 

Nonguideline Sediment Life Cycle Toxicity Test with 

Freshwater Invertebrates (Chironomus 

dilutus or C. tentans) 

TGAI 24 

Nonguideline Sediment Life Cycle Toxicity Test with 

Freshwater Invertebrates (Hyalella azteca) 

TGAI 24 

Imazalil Sulfate – PC Code 111902 

835.1410 Laboratory Volatility10 TEP 12 

835.4100 Aerobic Soil Metabolism TGAI or 

PAIRA 

24 

835.6100 Terrestrial Field Dissipation TGAI 24 

850.1075 Fish Acute Toxicity Test (saltwater only) TGAI 12 

850.1400 Fish Early-Life Stage Toxicity Test 

(freshwater) TGAI 12 

 

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 This study is required for both antimicrobial and conventional pesticide uses. All other studies listed in this table 

are for conventional pesticide uses. 

8

 This study is required for use in conducting risk assessments for workers contacting treated ornamental plants in 

greenhouses. The requested test material is imazalil (PC Code 111901). 9

 EPA does not have a guideline for the honeybee acute oral study. However, the OECD 213 guideline could be used 

for protocol development. A protocol must be submitted to the Agency for review and approval prior to study 

inception. The draft protocol must be submitted to the Agency within 90 days of receipt of this DCI. 10 Required as Henry’ Law Constant > 10-6 atm·m3

·mol-1 and to support greenhouse use (see problem formulation). 

Study must be performed at a pH above 7. 
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Table 1: Planned Data Needs for the Imazalil & Imazalil Sulfate Registration Review 4

Guideline 

Number5 Study Title Test Material 

Estimated 

Timeframe 

(Months 

from receipt 

of DCI) 

850.1730 Fish Bioconcentration Factor TGAI 12 

850.2100 Avian Acute Oral Toxicity (passerine 

species) TGAI 12 

850.3020 Honeybee Acute Contact Toxicity TGAI 12 

850.6100 Environmental Chemistry Method and 

Associated Independent Laboratory 

Validation (soil only) 

TGAI 12 

870.3465 90-day Inhalation Toxicity - Rat11 TGAI 24 

Nonguideline Honeybee Acute Oral Toxicity12

TGAI 12 

Nonguideline Whole Sediment Life Cycle Toxicity Test 

with Estuarine Invertebrates 

TGAI 24 

Nonguideline Sediment Life Cycle Toxicity Test with 

Freshwater Invertebrates (Chironomus 

dilutus or C. tentans) 

TGAI 24 

Nonguideline Sediment Life Cycle Toxicity Test with 

Freshwater Invertebrates (Hyalella azteca) 

TGAI 24 

Outstanding Data Requirements (for Imazalil) from GDCI-111901-2168313

860.1340 Residue Analytical Method (ILV-livestock 

commodities) 14

Residue of 

Concern 

Data received 

and currently 

in review 

TGAI = technical grade active ingredient; TEP = typical end-use product 

 

 

11 This study is required for both antimicrobial and conventional pesticide uses. All other studies listed in this table 

are for conventional pesticide uses. 

12 EPA does not have a guideline for the honeybee acute oral study. However, the OECD 213 guideline could be 

used for protocol development. A protocol must be submitted to the Agency for review and approval prior to study 

inception. The draft protocol must be submitted to the Agency within 90 days of receipt of this DCI. 13 The study listed in this section was previously required through a generic data call-in issued in April, 2005 and is 

still outstanding. This study will not be included in the anticipated Registration Review DCI because it is already 

required through the earlier DCI. 14 Only an ILV is required. An adequate residue analytical method is available for determining the total toxic 

residues of imazalil in/on plant commodities but not in livestock commodities. 
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RISK ASSESSMENTS FOR REGISTRATION REVIEW

During registration review, the Agency anticipates the need to conduct a comprehensive 

ecological risk assessment, including an endangered species assessment, for all uses of imazalil 

and imazalil sulfate. For human health, EPA anticipates the need to conduct revised dietary and 

occupational risk assessments during registration review. If toxicological endpoints or points of 

departure are revised based on the data that are anticipated to be required for registration review, 

they will be considered in the new assessments, as well as any changes to the standard operating 

procedures or default exposure assumptions. 

Table 2 below summarizes the planned registration review risk assessments based on the imazalil 

Problem Formulation and Scoping Document and the planned assessments have not changed 

from what was included in the PWP. 

Table 2: Planned Risk Assessments for the Imazalil & Imazalil Sulfate Registration Review 

Type of Risk Assessment Conduct? Notes 

Ecological and Environmental Fate 

Comprehensive ecological 

(species to be assessed 

include terrestrial and aquatic 

organisms), including 

endangered species 

Yes Assessments are needed for both imazalil and imazalil 

sulfate. 

Incidents Will check for 

updates 

There are no reported ecological incidents for imazalil 

or imazalil sulfate. 

Human Health 

Dietary 

Food Yes HED may need to update the dietary exposure 

estimates with more recent monitoring data for citrus 

commodities than the percent crop treated information 

and monitoring data used in HED’s dietary 

assessment for the 2003 RED. 

Drinking water Yes A new drinking water assessment will be needed to 

incorporate the use of the most current drinking water 

models. At the time of registration review, HED will 

include any updates in the modeled drinking water 

residues in the new dietary exposure assessment. 

Occupational 

Handlers (mixers, loaders, 

applicators) 

Yes Updated occupational handler exposure assessments 

will be required under registration review based on 

revisions to the Agency’s scenario-specific surrogate 

handler exposure data and updated exposure 

assessment methodologies. 
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Table 2: Planned Risk Assessments for the Imazalil & Imazalil Sulfate Registration Review 

Type of Risk Assessment Conduct? Notes 

Post-application Yes Chemical-specific data to evaluate post-application 

exposure associated with the greenhouse uses on 

ornamentals are needed to support registration review. 

The information/data will be incorporated into a 

revised post-application exposure and risk assessment 

for occupational workers. 

Residential 

Handlers No There are no registered residential uses for imazalil. 

Post-application No There are no registered residential uses at this time. 

However, residential exposures from off-site transport 

(e.g., spray drift or volatilization) may occur as a 

result of imazalil applications to agricultural fields. 

The Agency may conduct a spray drift assessment and 

examine the need for a volatilization assessment for 

imazalil during Registration Review. 

Other 

Aggregate Yes Evaluates the combined risk from dietary and 

residential exposures. During registration review, 

updated aggregate assessments will be needed to 

include any potential updates to exposure from food 

and drinking water, revised regulatory endpoints, 

points of departure (PoDs) and uncertainty 

factors/safety factors (UF/SFs). 

Cumulative No Imazalil is not a member of a cumulative group and 

no cumulative risk assessment is planned. 

Tolerances Yes Tolerances for residues of imazalil and imazalil 

sulfate are established in 40 CFR § 180.413; the 

tolerance expression will be revised to reflect current 

policy. Harmonization may not be possible due to 

differences in residues of concern for enforcement 

purposes. 

Incidents Will check for 

updates 

For a discussion of reported human incidents for 

imazalil and imazalil sulfate, see page 14 of the 

Scoping Document and the Imazalil and Imazalil 

Sulfate: Tier I Review of Human Incidents. 
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TIMELINE

EPA has created the following estimated timeline for the completion of the imazalil registration 

review in Table 3 below. The projected timeline has not changed since the PWP. 

Table 3: Registration Review for Imazalil and Imazalil Sulfate – Projected Registration 

Review Timeline

Activities Estimated Date 

Opening the Docket 

Open Docket and 60-day Public Comment Period Dec. 2013 – 

Completed 

Close Public Comment Feb. 2014 – 

Completed 

Case Development 

Final Work Plan June 2014 - 

Completed 

Issue DCI 2014: July – Sept. 

Data Submission 2016: July – Sept. 

60-day Public Comment Period for Draft Risk Assessments7[1] 2018: Jan. - March 

Registration Review Decision 

60-day Public Comment Period for Proposed Registration Review 

Decision 

2018: Oct. – Dec. 

Registration Review Decision and Begin Post-Decision Follow-up 2019 

Total (years) 6 

NEXT STEPS 

As noted previously, the Agency plans to require several environmental fate, ecological effects, 

and human health studies for imazalil through a Data Call-In Notice, expected to be issued in the 

fall of 2014. 

 

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 The regulations governing Registration Review generally require the Agency to provide a public comment period 

of at least 30 calendar days for draft risk assessments; see 40 CFR Part 155.53(c). For conventional pesticides, the 

Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments.